Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Cape Town , South Africa.
Expert Opin Drug Saf. 2019 Oct;18(10):875-882. doi: 10.1080/14740338.2019.1648429. Epub 2019 Aug 5.
: Outcomes of treatment for resistant tuberculosis are poor, with long treatment duration and poor tolerability. Bedaquiline is a novel anti-mycobacterial drug, which has a very long terminal elimination half-life. Bedaquiline was approved in 2012 for drug-resistant tuberculosis following improved time to culture conversion and cure rates in a phase 2b study; but mortality was higher in the bedaquiline arm, resulting in a black box warning despite the fact that almost all deaths occurred after bedaquiline was stopped. : The authors review safety data of bedaquiline used for rifampicin-resistant tuberculosis from the phase 2 studies, and from case series and observational cohorts. The authors focus on QT interval prolongation, hepatotoxicity, and mortality. : Bedaquiline markedly reduced mortality and improved treatment success in observational studies, resulting in bedaquiline being strongly recommended for rifampicin-resistant tuberculosis by the World Health Organization. In the phase 2 studies participants randomised to bedaquiline had higher rates of liver enzyme elevation and modest QT interval prolongation. Severe QT prolongation was an infrequent cause of bedaquiline interruption despite the frequent use of concomitant drugs that also prolong the QT interval. While awaiting results of phase 3 randomised controlled trials, tuberculosis treatment programmes should strengthen pharmacovigilance.
治疗耐药结核病的效果较差，治疗时间长，耐受性差。贝达喹啉是一种新型抗分枝杆菌药物，其终末消除半衰期很长。贝达喹啉于 2012 年在一项 2b 期研究中显示改善了培养转换时间和治愈率后被批准用于耐药结核病；但贝达喹啉组的死亡率更高，尽管几乎所有的死亡都发生在停止使用贝达喹啉之后，但仍有黑框警告。
作者回顾了 2 期研究、病例系列和观察性队列中用于耐利福平结核病的贝达喹啉的安全性数据。作者重点关注 QT 间期延长、肝毒性和死亡率。
贝达喹啉在观察性研究中显著降低了死亡率并提高了治疗成功率，因此世界卫生组织强烈推荐将其用于耐利福平结核病。在 2 期研究中，随机接受贝达喹啉的参与者肝酶升高的发生率较高，QT 间期略有延长。尽管经常同时使用也会延长 QT 间期的药物，但严重的 QT 间期延长并不是导致贝达喹啉中断的常见原因。在等待 3 期随机对照试验结果的同时，结核病治疗方案应加强药物警戒。
